EGFR heterogeneity and implications for therapeutic intervention in glioblastoma

Eskil Eskilsson; Gro V Røsland; Gergely Solecki; Qianghu Wang; Patrick N Harter; Grazia Graziani; Roel G W Verhaak; Frank Winkler; Rolf Bjerkvig; Hrvoje Miletic

doi:10.1093/neuonc/nox191

EGFR heterogeneity and implications for therapeutic intervention in glioblastoma

Neuro Oncol. 2018 May 18;20(6):743-752. doi: 10.1093/neuonc/nox191.

Authors

Eskil Eskilsson¹, Gro V Røsland², Gergely Solecki³, Qianghu Wang^{1

4}, Patrick N Harter⁵, Grazia Graziani⁶, Roel G W Verhaak^{1

4

7}, Frank Winkler³, Rolf Bjerkvig^{2

8

9}, Hrvoje Miletic^{2

8

10}

Affiliations

¹ Department of Genomic Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
² Department of Biomedicine, University of Bergen, Norway.
³ Department of Neurooncology, University Hospital Heidelberg, Germany.
⁴ Department of Bioinformatics and Computational Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
⁵ Edinger-Institute, Goethe-University Medical School, Frankfurt am Main, Germany.
⁶ Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
⁷ The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
⁸ KG Jebsen Brain Tumor Research Center, University of Bergen, Norway.
⁹ Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg.
¹⁰ Department of Pathology, Haukeland University Hospital, Bergen, Norway.

Abstract

Patients with glioblastoma (GBM) have a universally poor prognosis and are in urgent need of effective treatment strategies. Recent advances in sequencing techniques unraveled the complete genomic landscape of GBMs and revealed profound heterogeneity of individual tumors even at the single cell level. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed in clinical trials. In this review, we discuss the clonal and functional heterogeneity of EGFRs in GBM development and critically reassess the potential of EGFRs as therapeutic targets.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

ErbB Receptors / antagonists & inhibitors
ErbB Receptors / genetics
Glioblastoma / drug therapy*
Glioblastoma / genetics*
Glioblastoma / pathology
Humans
Molecular Targeted Therapy*
Mutation*
Prognosis
Protein Kinase Inhibitors / therapeutic use*

Substances

Protein Kinase Inhibitors
EGFR protein, human
ErbB Receptors